NEW YORK (Reuters Health) - Babies born to mothers who took
anti-tumor necrosis factor (anti-TNF) agents during pregnancy
have detectable drug in their bodies up to 12 months of age, new
findings show.

These infants should therefore not receive live vaccines
during their first year of life, Dr. Mette Julsgaard of Aarhus
University Hospital in Denmark and her colleagues concluded in a
report online April 7 in Gastroenterology.

Many women with inflammatory bowel disease (IBD) require
treatment with anti-TNF drugs during pregnancy, Dr. Julsgaard
and her team note. They add that while studies have so far not
linked in utero exposure to adverse neonatal outcomes, there is
little data on how infants clear the drug and whether exposure
may affect childhood development.

To investigate, the researchers looked at 80 mother-baby
pairs from Denmark, Australia and New Zealand. Thirty-six of the
mothers received adalimumab during pregnancy, 44 infliximab, and
39 also received thiopurines.

Median duration of anti-TNF treatment was 2.5 years. Women
on adalimumab received their last pregnancy dose at median
gestational week (GW) 35, while the last dose of infliximab was
given at median GW 30. Thirty-eight women had a disease relapse
while pregnant, while 42 remained in remission.

Cord blood concentrations of anti-TNF agents were higher
than maternal concentrations, with a median ratio of infant to
maternal concentration at birth of 1.21 for adalimumab and 1.97
for infliximab. Both maternal and cord blood concentrations were
inversely correlated with duration since last exposure.

Eight of the babies exposed to adalimumab (22%) had no
detectable level of the drug in their cord blood, while
infliximab was detected at birth in all of the exposed infants.
Mean time to clearance was 4 months with adalimumab and 7.3
months with infliximab. One infant had detectable levels of
infliximab at 12 months, which were cleared by age 15 months.

Four infants developed bacterial infections during their
first year, while 16 had viral infections, all of which had
benign courses. The relative risk of any infection was 2.7 for
infants born to mothers who received both an anti-TNF agent and
thiopurine, compared to those on anti-TNF monotherapy.

"It is reassuring that all infant infections had a benign
course. Still, combination therapy in pregnant women should be
carefully counterbalanced between risk of disease activity in
pregnancy (if thiopurine is discontinued) and thereby increased
risk of adverse pregnancy outcome such as preterm birth and
small for gestational age, and an increased risk of infection in
the offspring if combination therapy is continued," Dr.
Julsgaard told Reuters Health via e-mail. "Therefore pregnant
women on combination therapy should receive thorough
counseling."

The risk of live vaccines for infants born to mothers on
anti-TNF agents probably outweighs the benefit, the researcher
added. "However at one year of age, infants exposed to
anti-TNF-alpha in utero can receive live vaccines such as
measles, mumps and rubella and varicella in order to protect
the infant from potentially severe illness."